EGFR Biomarker

Epidermal growth factor receptor (EGFR) is a receptor located on the cell surface. EGFR binds epidermal growth factor (EGF) resulting in turning “on,” or activating the downstream signaling pathway.  

The signaling pathway can be thought of as a chain of dominoes. EGF binding to EGFR is like the first domino to fall, triggering a chain reaction. Like the domino effect, the activation of the receptor (EGF binding to EGFR) results in the activation of downstream proteins RAS, RAF, MEK, and ERK in a signaling cascade. This pathway controls normal cell processes, such as cell growth, proliferation (division), and survival.  

While EGFR itself isn’t necessarily a biomarker in colorectal cancer, there are multiple biomarkers that can influence the EGFR signaling pathway and act as predictive biomarkers for response to EGFR inhibitor treatments. These biomarkers include KRAS, NRAS, BRAF, and HER2, and they are determined from tumor tissue and even blood. 

EGFR inhibitors, also called anti-EGFR therapies, block the EGFR protein in an attempt to slow or stop the growth of cancer cells.   

Cetuximab and panitumumab are FDA-approved EGFR inhibitors for the treatment of metastatic colorectal cancer. These agents are not chemotherapies, but what we call biologic agents. These therapies are given as IV every two weeks usually with chemotherapy. They are monoclonal antibody therapies and work by binding the EGFR protein. With the antibodies bound to EGFR, there is nowhere for EGF to bind. Therefore, the downstream pathways cannot be activated.  

Biomarker testing is a great way to know if you are more or less likely to respond to EGFR targetable therapies.  

Patients with wild-type KRAS/NRAS/BRAF often benefit from targeted treatment with EGFR inhibitors, while mutant KRAS/NRAS/BRAF is an indicator that EGFR inhibitor will not be effective. Why not? EGFR inhibitors block EGFR. Mutant RAS/BRAF proteins are often always turned “on” or constitutively active. So, even if EGFR is inhibited by targeted therapies, mutant RAS/BRAF proteins will still be “on” or active.

The most effective treatment varies by individual. It is best to speak with your medical team to learn more about the best treatment options for you. However, knowing your biomarkers is a great place to start when deciding whether or not to try an EGFR inhibitor.  

Check out Fight CRC’s Clinical Trial Finder and our blog series, Clinical Trial Conversations, to research and discover more.